The primary goal of the proposed research is to elucidate the cellular mechanisms responsible for hydrostatic pressure effects on electromechanical activity in cardiac muscle. Our previous work has demonstrated that hydrostatic pressure per se acting directly on the excitable membrane of heart cells alters normal patterns of impulse initiation and distribution throughout the myocardium. In the extreme case these effects are arrhythmogenic and potentially fatal to diving man. Additional risk factors such as fast heart rate and hypothermia exascerbate the depressant effects of high hydrostatic pressure. The inotropic effects of pressure are no less important in determining adjustments in cardiac function during exposure to hyperbaric environments. The direct effects of pressure on mechanical performance however are yet to be revealed. We are now proposing an extensive series of experiments to delineate underlying mechanisms for pressure sensitive cardiac phenomena at the cellular and subcellular levels of organization. Modern electrophysiological techniques will be employed to determine the relative importance of membrance components such as membrane capacitance, resistance and ion pump activity. Pressure effects on mechanical activity will be studied with particular emphasis on the role of slow inward calcium current, cyclical turnover of intracellular calcium and direct effects on the regulatory and contractile proteins. Multifactor experiments to assess the important interactions between pressure and temperature will also be performed. The new information provided by these experiments should improve our understanding of cardiac muscle functions in general and have direct application with regard to the establishment of guidelines for safe, productive exposure to hyperbaric environments.